This project examines the use of a biocompatible and biologically inert biomaterial (polyvinyl alcohol (PVA) polymer) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the effectiveness of properties of this polymer and its effect on the heart muscle and mitral valve function so that it can be used in the most effective way in patients with ischemic mitral regurgitation. Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles late mortality. The fundamental mechanism underlying ischemic mitral regurgitation is distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We propose to explore an innovative approach toward treating ischemic mitral regurgitation with the use of PVA polymer that has been specifically designed for injection into the myocardium with subsequent crosslinking once injected. This results in myocardial tissue bulking and repositioning of the infarcted myocardial wall with relief of LV distortion and deformation, thereby restoring mitral valve function. We plan a parallel approach of polymer material application and development with long- term in vitro testing of polymer and in vivo experimental studies using an established ovine model of ischemic mitral regurgitation. The in vivo animal experimentation will investigate the main therapeutic endpoint which effectiveness of PVA polymer injection in reducing ischemic mitral regurgitation. The in-vivo experiments will also address the biomechanical and physiological effects of the polymer injection in the beating heart with the use of hemodynamic monitoring, quantitative 3D echocardiography and sonomicrometry. MRI diffusion imaging will assess regional changes, if any, of myocardial fiber architecture. The physical and mechanical characteristics of PVA polymer will be optimized in an iterative fashion, based on data and feedback from the in-vivo animal experiments. Similarly, data from PVA testing will be shared to optimize the in-vivo application. This information sharing, inherent in the parallel design of this proposal, will foster the collaborative efforts of this multidisciplinary team. PUBLIC HEALTH RELEVANCE: This grant examines an important and common cardiac valve disorder, ischemic mitral regurgitation, for which the therapies are invasive and inconsistent. The public health effects of ischemic mitral regurgitation are significant as it affects up to 20 to 30% of patients following a heart attack and up to 50% of patients with heart failure due to a cardiomyopathy. The presence of this valvular disorder is associated with a poor prognosis, doubling mortality when present. The purpose of this grant is to explore novel and less invasive therapies to treat this important valve disorder.